‘Sex’ in the cancer cell

Lafta, Inam J.; Bryant, Helen E.; Goldman, Alastair S. H.

doi:10.18632/oncotarget.2355

Cited by 6 publications

(7 citation statements)

References 7 publications

(10 reference statements)

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“…These chromosomal segregation events differ considerably to those of the first meiotic division during gametogenesis, where homologous chromosomes of a diploid germline progenitor cell conjoin via programmed genetic recombination intermediates to form a bivalent, which is ultimately resolved, culminating in a reductional chromosome segregation event and "shuffled" genetic material (2,3). There is now solid emerging evidence to support the concept that the inappropriate activation of meiotic chromosome regulator genes in mitotically dividing somatic cells results in deviations in mechanisms controlling chromosome maintenance and segregation (4)(5)(6)(7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

Meiosis-like Functions in Oncogenesis: A New View of Cancer

McFarlane

Wakeman

2017

Cancer Research

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Cancer cells have many abnormal characteristics enabling tumors to grow, spread, and avoid immunologic and therapeutic destruction. Central to this is the innate ability of populations of cancer cells to rapidly evolve. One feature of many cancers is that they activate genes that are normally associated with distinct developmental states, including germ cell–specific genes. This has historically led to the proposal that tumors take on embryonal characteristics, the so called embryonal theory of cancer. However, one group of germline genes, not directly associated with embryonic somatic tissue genesis, is the one that encodes the specific factors to drive the unique reductional chromosome segregation of meiosis I, which also results in chromosomal exchanges. Here, we propose that meiosis I–specific modulators of reductional segregation can contribute to oncogenic chromosome dynamics and that the embryonal theory for cancer cell growth/proliferation is overly simplistic, as meiotic factors are not a feature of most embryonic tissue development. We postulate that some meiotic chromosome-regulatory functions contribute to a soma-to-germline model for cancer, in which activation of germline (including meiosis) functions drive oncogenesis, and we extend this to propose that meiotic factors could be powerful sources of targets for therapeutics and biomonitoring in oncology. Cancer Res; 77(21); 5712–6. ©2017 AACR.

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Section: Introductionmentioning

confidence: 99%

Meiosis-like Functions in Oncogenesis: A New View of Cancer

McFarlane

Wakeman

2017

Cancer Research

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“…To date, most of the CT genes whose expression has been studied are located on the X chromosome (X-CT genes) and belong to large paralogous gene families [ 2 - 4 ]. Recently, a computational pipeline combining expressed sequence tag and microarray meta-analyses of the human orthologues of mouse spermatocyte-specific genes revealed a large cohort of new CT genes that were expressed in a broad spectrum of cancer types [ 25 - 29 ]. Unlike the X-CT genes, the majority of these genes are autosomally encoded and are single copy.…”

Section: Introductionmentioning

confidence: 99%

Identification of a class of human cancer germline genes with transcriptional silencing refractory to the hypomethylating drug 5-aza-2ˈ-deoxycytidine

et al. 2014

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Bona fide germline genes have expression restricted to the germ cells of the gonads. Testis-specific germline development-associated genes can become activated in cancer cells and can potentially drive the oncogenic process and serve as therapeutic/biomarker targets; such germline genes are referred to as cancer/testis genes. Many cancer/testis genes are silenced via hypermethylation of CpG islands in their associated transcriptional control regions and become activated upon treatment with DNA hypomethylating agents; such hypomethylation-induced activation of cancer/testis genes provides a potential combination approach to augment immunotherapeutics. Thus, understanding cancer/testis gene regulation is of increasing clinical importance. Previously studied cancer/testis gene activation has focused on X chromosome encoded cancer/testis genes. Here we find that a sub-set of non-X encoded cancer/testis genes are silenced in non-germline cells via a mechanism that is refractory to epigenetic dysregulation, including treatment with the hypomethylating agent 5-aza-2′-deoxycytidine and the histone deacetylase inhibitor tricostatin A. These findings formally indicate that there is a sub-group of the clinically important cancer/testis genes that are unlikely to be activated in clinical therapeutic approaches using hypomethylating agents and it indicates a unique transcriptional silencing mechanism for germline genes in non-germline cells that might provide a target mechanism for new clinical therapies.

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“…Thus, much of our understanding of these processes is extrapolative in nature. Despite these constraints, it is becoming clear that activation of meiotic genes (and other germ line genes) occurs during oncogenesis and that these genes provide functions for both initiation and maintenance of the cancerous state in a range of cancer types (Simpson et al ., ; Fratta et al ., ; Rousseaux et al ., ; Lafta et al ., ; McFarlane et al ., , ; Whitehurst, ; Nielsen & Gjerstorff, ). It is an emerging possibility that meiotic deregulation is a feature of germ cell (GC) tumours (for example, see Jørgensen et al ., ).…”

Section: Introductionmentioning

confidence: 98%

Meiotic gene activation in somatic and germ cell tumours

Feichtinger

McFarlane

2019

Andrology

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Background Germ cell tumours are uniquely associated with the gametogenic tissues of males and females. A feature of these cancers is that they can express genes that are normally tightly restricted to meiotic cells. This aberrant gene expression has been used as an indicator that these cancer cells are attempting a programmed germ line event, meiotic entry. However, work in non‐germ cell cancers has also indicated that meiotic genes can become aberrantly activated in a wide range of cancer types and indeed provide functions that serve as oncogenic drivers. Here, we review the activation of meiotic factors in cancers and explore commonalities between meiotic gene activation in germ cell and non‐germ cell cancers. Objectives The objectives of this review are to highlight key questions relating to meiotic gene activation in germ cell tumours and to offer possible interpretations as to the biological relevance in this unique cancer type. Materials and Methods PubMed and the GEPIA database were searched for papers in English and for cancer gene expression data, respectively. Results We provide a brief overview of meiotic progression, with a focus on the unique mechanisms of reductional chromosome segregation in meiosis I. We then offer detailed insight into the role of meiotic chromosome regulators in non‐germ cell cancers and extend this to provide an overview of how this might relate to germ cell tumours. Conclusions We propose that meiotic gene activation in germ cell tumours might not indicate an unscheduled attempt to enter a full meiotic programme. Rather, it might simply reflect either aberrant activation of a subset of meiotic genes, with little or no biological relevance, or aberrant activation of a subset of meiotic genes as positive tumour evolutionary/oncogenic drivers. These postulates provide the provocation for further studies in this emerging field.

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‘Sex’ in the cancer cell

Cited by 6 publications

References 7 publications

Meiosis-like Functions in Oncogenesis: A New View of Cancer

Meiosis-like Functions in Oncogenesis: A New View of Cancer

Identification of a class of human cancer germline genes with transcriptional silencing refractory to the hypomethylating drug 5-aza-2ˈ-deoxycytidine

Meiotic gene activation in somatic and germ cell tumours

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